The Developmental Therapeutics Program evolved from the more basic Cell Cycling and Signaling Program, which scored Outstanding in prior renewal cycles ofthis Helen Diller Family Comprehensive Cancer Center support grant. The research themes ofthe Cell Cycling and Signaling Program were related to identification and validation of therapeutic targets. Many of these targets have subsequently moved into preclinical testing or are ready to be explored in early-stage clinical trials. The new Eariy Phase Clinical Trials Unit has created an ideal opportunity to translate these themes effectively, through the design and analysis of innovative research protocols. The Program comprises 32 members involving 13 different departments and brings together basic cancer biologists and physician scientists with the common goal of discovering and testing novel compounds and treatment strategies for cancer The Program themes are: 1) Targeting signal transduction pathways (RTKs, RAS, RAF/MAPK, Pl 3' kinase, and wnt) 2) Targeting DNA replication and genome integrity (cell cycle, telomerase, HDAC) 3) Angiogenesis 4) Apoptosis 5) Genetic determinants of sensitivity and resistance The wide range of expertise ofthe Program members will mutually enrich and complement the discoveries of individual investigators with the overall Program goal being to accelerate the transition from drug discovery to the approval of more effective and less toxic drugs for patients with cancer. Research in the Program spans from drug discovery, cell signaling, molecular pathology and bioimaging to pharmacogenomics, as well as clinical and population science with recent high impact publications in Nature, Nature Medicine, Nature Genetics, New England Journal of Medicine, Journal of Clinical Oncology, Journal of Biological Chemistry, JAMA, Proceedings of the National Academy of Science of the United States, and The Lancet. The Program has a sizable and increasing percentage of intra- and inter-programmatic publications, which reflect the thematic breadth of the work and the emerging efforts of strategic integration of its members. The Program had $7,271,609 total peer-reviewed support for the last budget year. The Program has 12% intra-programmatic and 13% inter-programmatic publications.